DEVELOPMENT AND VALIDATION OF THE METHOD FOR DETERMINATION OF RAMIPRIL AND HYDROCHLOROTHIAZIDE FOR THE STUDY OF DISSOLUTION PROFILES

Abstract

Introduction. When developing generic drugs, it is important to compare their dissolution profiles with the dissolution profiles of the original drug. Therefore, it is important to develop fast and sensitive methods for studying dissolution profiles.

The aim of the study – to develop and validate an analytical procedure for the simultaneous determination of ramipril and hydrochlorothiazide by liquid chromatography, which can be used to study the dissolution profiles of combined drugs.

Research Methods. The research used standard samples of ramipril and hydrochlorothiazide (USP RS), class A reagents, tablets of Ramipril with Hydrochlorothiazide 2.5 mg/12.5 mg and 10 mg/25 mg. The samples were analyzed on a liquid chromatograph with an Agilent 1260 diode array detector. An Inertsil ODS-3 column (4.6 × 150 × 3 μm) was used; mobile phase A – 0.2 g/l sodium hexanesulfonate solution (pH 2.7); mobile phase B: acetonitrile; mobile phase speed 1.5 ml/min; detection wavelength - 210 nm; column temperature – 45 °C, gradient elution mode.

Results and Discussion. A technique for the simultaneous determination of ramipril and hydrochlorothiazide by liquid chromatography in 4 dissolution media (0.1 M hydrochloric acid solution and buffer solutions of pH 1.2, pH 4.5, and pH 6.8) was developed. The developed method has sufficient linearity, accuracy and precision and is robust to minor changes in chromatography conditions. The sensitivity of the method is 0.2 μg/ml for ramipril and 0.4 μg/ml for hydrochlorothiazide. The studied range allows using the method for dosages from 2.5 to 10 mg of ramipril and from 12.5 to 25 mg of hydrochlorothiazide.

Conclusions. The developed technique can be used for simultaneous determination of ramipril and hydrochlorothiazide to study dissolution profiles of the combined dosage form.